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Article: Glial cell line-derived neurotrophic factor family receptors are abnormally expressed in aganglionic bowel of a subpopulation of patients with Hirschsprung's disease

TitleGlial cell line-derived neurotrophic factor family receptors are abnormally expressed in aganglionic bowel of a subpopulation of patients with Hirschsprung's disease
Authors
Issue Date2002
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/
Citation
Laboratory Investigation, 2002, v. 82 n. 6, p. 703-711 How to Cite?
AbstractHirschsprung's disease (HSCR), a congenital disease, is characterized by the absence of ganglion cells in the ganglion plexuses of the caudal most gut. In the aganglionic colon, the plexus remnants are replaced by aggregates of glial cells and hypertrophied nerve fibers. Signaling of glial cell line-derived neurotrophic factor (GDNF)-GFRAs-receptor tyrosine kinase (RET) is crucial for the development and maintenance of ganglion cells. Mutations of genes such as GDNF and RET lead to the perturbation of this signaling pathway, which causes HSCR. To understand the role of GFRAs in ganglion cells and the pathogenesis of HSCR, we intended to determine the specific cell lineages in the enteric nervous system that normally express GFRAs but are affected in HSCR. We studied colon biopsy specimens from 13 patients with HSCR (aged 1 day to 38 months) and 6 age-matched patients without HSCR as normal controls. RT-PCR, in situ hybridization, and immunohistochemistry were performed to examine the expression and cellular distributions of GFRAs in resected bowel segments of normal infants and those with HSCR. In normal infants and normoganglionic colon of patients with HSCR, the expression of GFRA1 was restricted to the glial cells and neurones of the ganglion plexuses. GFRAs expression was found to be markedly reduced in the aganglionic colons of 3 infants with HSCR but was unaffected in the aganglionic colons of 10 other infants with HSCR. Residual GFRA expression was restricted to enteric glial cells in the plexus remnants of the aganglionic colons. Hypertrophied nerve fibers were not found to express GFRA1. We provide the first evidence that abnormal expression of GFRAs in the enteric nervous system may be involved in the pathogenesis of HSCR in a subpopulation of patients.
Persistent Identifierhttp://hdl.handle.net/10722/68181
ISSN
2015 Impact Factor: 4.202
2015 SCImago Journal Rankings: 2.133
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorSamy, ETen_HK
dc.contributor.authorSham, MHen_HK
dc.contributor.authorMulligan, LMen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2010-09-06T06:02:07Z-
dc.date.available2010-09-06T06:02:07Z-
dc.date.issued2002en_HK
dc.identifier.citationLaboratory Investigation, 2002, v. 82 n. 6, p. 703-711en_HK
dc.identifier.issn0023-6837en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68181-
dc.description.abstractHirschsprung's disease (HSCR), a congenital disease, is characterized by the absence of ganglion cells in the ganglion plexuses of the caudal most gut. In the aganglionic colon, the plexus remnants are replaced by aggregates of glial cells and hypertrophied nerve fibers. Signaling of glial cell line-derived neurotrophic factor (GDNF)-GFRAs-receptor tyrosine kinase (RET) is crucial for the development and maintenance of ganglion cells. Mutations of genes such as GDNF and RET lead to the perturbation of this signaling pathway, which causes HSCR. To understand the role of GFRAs in ganglion cells and the pathogenesis of HSCR, we intended to determine the specific cell lineages in the enteric nervous system that normally express GFRAs but are affected in HSCR. We studied colon biopsy specimens from 13 patients with HSCR (aged 1 day to 38 months) and 6 age-matched patients without HSCR as normal controls. RT-PCR, in situ hybridization, and immunohistochemistry were performed to examine the expression and cellular distributions of GFRAs in resected bowel segments of normal infants and those with HSCR. In normal infants and normoganglionic colon of patients with HSCR, the expression of GFRA1 was restricted to the glial cells and neurones of the ganglion plexuses. GFRAs expression was found to be markedly reduced in the aganglionic colons of 3 infants with HSCR but was unaffected in the aganglionic colons of 10 other infants with HSCR. Residual GFRA expression was restricted to enteric glial cells in the plexus remnants of the aganglionic colons. Hypertrophied nerve fibers were not found to express GFRA1. We provide the first evidence that abnormal expression of GFRAs in the enteric nervous system may be involved in the pathogenesis of HSCR in a subpopulation of patients.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/labinvest/en_HK
dc.relation.ispartofLaboratory Investigationen_HK
dc.subject.meshColon - innervation - metabolism - pathology-
dc.subject.meshDrosophila Proteins-
dc.subject.meshHirschsprung Disease - metabolism - pathology-
dc.subject.meshProto-Oncogene Proteins - genetics - metabolism-
dc.subject.meshReceptor Protein-Tyrosine Kinases - genetics - metabolism-
dc.titleGlial cell line-derived neurotrophic factor family receptors are abnormally expressed in aganglionic bowel of a subpopulation of patients with Hirschsprung's diseaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0023-6837&volume=82&issue=6&spage=703&epage=711&date=2002&atitle=Glial+cell+line-derived+neurotrophic+factor+family+receptors+are+abnormally+expressed+in+aganglionic+bowel+of+a+subpopulation+of+patients+with+Hirschsprung%27s+diseaseen_HK
dc.identifier.emailLui, VCH: vchlui@hkucc.hku.hken_HK
dc.identifier.emailSham, MH: mhsham@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authoritySham, MH=rp00380en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1097/01.LAB.0000017364.13014.AE-
dc.identifier.pmid12065680-
dc.identifier.scopuseid_2-s2.0-0036278689en_HK
dc.identifier.hkuros68095en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036278689&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume82en_HK
dc.identifier.issue6en_HK
dc.identifier.spage703en_HK
dc.identifier.epage711en_HK
dc.identifier.isiWOS:000176317600004-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridSamy, ET=6602891563en_HK
dc.identifier.scopusauthoridSham, MH=7003729109en_HK
dc.identifier.scopusauthoridMulligan, LM=7005138824en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK

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